PROJECT SUMMARY/ABSTRACT The proposed research project will address two fundamental research questions about information processing in the biological brain. We will begin addressing this question by focusing on how the hippocampus accumulates different spatial maps (i.e. linear tracks) across a lifetime by a novel i imaging technique, the wire- free miniature microscope (Miniscope), for long-term in vivo calcium imaging in untethered, freely behaving animals. We will investigate the question of orthogonal vs. integrated coding of spatial maps and their impact on memory capacity and efficiency in young adult mice. Does learning new (more) maps increase the efficiency of neural encoding, such that there are fewer cells encoding redundant spatial information? Is a decreasing number of cells required to encode each subsequent map to prevent the hippocampus from reaching capacity? Can we calculate the memory capacity of a particular network or of the hippocampus overall? Next, to explore the question of how these processes may change across a lifetime, we will investigate whether or not the same rules for coding spatial maps apply in middle aged mice with varying number of memories for different linear tracks previously accumulated. As we age, is there simply less ?available space? in our brains as many of the neuronal resources have been taken up by the previous memories accumulated across a lifetime and, consequently, more competition for the neural resources required to encode new information? Is generalization, at least in part, a consequence of a change in storage strategy, where details are dropped in order to maximize efficiency. We will use state of the art modeling techniques as well as causal biological manipulations to probe these questions. Answering these questions regarding how the brain optimizes storage capacity for information will contribute to better understanding a broad spectrum of brain disorders that have problems with relational memory, including Schizophrenia, Depression, Dementia, Alzheimer's disease. Furthermore, by understanding the rules the brain uses to optimize storage capacity and perform efficiently, these rules and principles can be applied to developing neuroprosthetics that can treat patients with brain damage, including stroke, epilepsy, traumatic brain injury.